Research

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Paola Storici


Paola Storici
 Curriculum vitae:
Degree in Medicinal Chemistry, University of Trieste.
PhD in Biochemistry, University of Trieste.
Postdoctoral Fellow, Structural Biology, Biozentrum - Basel.
Senior Scientist, R&D Oncology, Pharmacia - Milano.
Head of Biochemistry, R&D Nerviano Medical Sciences - Milano.

Current position:
Senior Research Scientist, Elettra - Sincrotrone Trieste.
Head of the Protein Production Facility


Contact details:
Address: Elettra - Sincrotrone Trieste S.C.p.A.
SS 14 - km 163,5 AREA Science Park
34149 Basovizza, Trieste, Italy
Tel: +39-040-3758854
Mobile: +39-331-1921484
Email: paola.storici@elettra.eu
Personal webpage: 

http://www.elettra.eu/PEOPLE/index.php?n=PaolaStorici.HomePage

The group has three main objectives:

  • Run the protein production facility to support research activity of public or private users 

  • Investigate biochemical and structural properties of protein targets for therapy of cancer and neurodegenerative diseases

  • Investigate structural properties of SARS-CoV-2 protein targets for identification of repourposed and novel drugs

     

The Protein Production Facility

A Protein Facility is acive since 2015 at the Elettra synchrotron of Trieste taking advantage of the infrastructures and of the expertise existing in the structural biology laboratory. The protein production platform is organized for expression in E.coli, insect cells and mammalian cell systems, and is well equipped to go from small-scale constructs screening to mid/large-scale preparations, with strong capacity and competence in protein purification techniques. On average we support about 30 different protein projects a year from internal and external groups of academic or industrial R&D partners. In particular the lab intent is to facilitate the process to obtain recombinant proteins suitable for analysis with synchrotron radiation techniques (x-ray diffraction, SAXS, FTIR). The active projects are distinguished between collaborative research projects, industrial services and tutoring activities. 

The main scientific interest is on protein targets for drug discovery with focus on treatments for cancer and neurodegenerative diseases. Most of the targets belong to two big proteins families of druggable targets: the human kinases and the deubiquitinases. In addition, our pipeline encompasses between different types of protein such as membrane proteins, proteases as well as nanobodies. The Facility is an active member of the P4EU Network (Protein Production and Purification Partnership in Europe; www.p4eu.org) and takes part in benchmarking activities to keep up with the state of the art of the protein production technology and to offer a validated process to partners. 

Liquid Handler System - Tecan Freedom Evo 150
Tecan Freedom EVO 150

 

Users in 2017Protein portfolio in 2017

Selected Publications

(*Corresponding author)
  • Minnelli, C.; Laudadio, E.; Sorci, L.; Sabbatini, G.; Galeazzi, R.; Amici, A.; Semrau, M.S.; Storici, P.; Rinaldi, S.; Stipa, P.; Marcaccio, M.; Mobbili G. (2022) Identification of a novel nitroflavone-based scaffold for designing mutant-selective EGFR tyrosine kinase inhibitors targeting T790M and C797S resistance in advanced NSCLC. Bioorganic Chemistry, 106219. https://doi.org/10.1016/j.bioorg.2022.106219
  • Semrau, M. S.; Giachin, G.; Covaceuszach, S.; Cassetta, A.; Demitri, N.; Storici, P.*; Lolli, G.* (2022) Molecular Architecture of the Glycogen- Committed PP1/PTG Holoenzyme. Nat Commun, 13 (1), 6199. https://doi.org/10.1038/s41467-022-33693-z.

  • Pelliccia, S.; Cerchia, C.; Esposito, F.; Cannalire, R.; Corona, A.; Costanzi, E.; Kuzikov, M.; Gribbon, P.; Zaliani, A.; Brindisi, M.; Storici, P.; Tramontano, E.; Summa, V.  (2022) Easy Access to α-Ketoamides as SARS-CoV-2 and MERS Mpro Inhibitors via the PADAM Oxidation Route. European Journal of Medicinal Chemistry, 114853. https://doi.org/10.1016/j.ejmech.2022.114853.

  • Balboni, B.; Tripathi, S. K.; Veronesi, M.; Russo, D.; Penna, I.; Giabbai, B.; Bandiera, T.; Storici, P.; Girotto, S.; Cavalli, A. (2022) Identification of Novel GSK-3β Hits Using Competitive Biophysical Assays. Int. J. Mol. Sci., 18. https://doi.org/10.3390/ijms23073856.

  • Demuro, S.; Sauvey, C.; Tripathi, S. K.; Di Martino, R. M. C.; Shi, D.; Ortega, J. A.; Russo, D.; Balboni, B.; Giabbai, B.; Storici, P.; Girotto, S.; Abagyan, R.; Cavalli, A. (2022) ARN25068, a Versatile Starting Point towards Triple GSK-3β/FYN/DYRK1A Inhibitors to Tackle Tau-Related Neurological Disorders. European Journal of Medicinal Chemistry, 229, 114054. https://doi.org/10.1016/j.ejmech.2021.114054.

  • Costanzi, E.; Kuzikov, M., Esposito, F., Albani, S., Demitri, N., Giabbai, B., Camasta, M., Tramontano, E., Rossetti, G., Zaliani, A., Storici, P. (2021). Structural and Biochemical Analysis of the Dual Inhibition of MG-132 against SARS-CoV-2 Main Protease (Mpro/3CLpro) and Human Cathepsin-L. International Journal of Molecular Sciences, 22 (21), 11779. https://doi.org/10.3390/ijms222111779.

  • Brullo C., Rapetti F., Abbate S., Prosdocimi T., Torretta A., Semrau M.S., Massa M., Alfei S., Storici P., Parisini E., Bruno O. (2021). Design, synthesis, biological evaluation and structural characterization of novel GEBR library PDE4D inhibitors. European Journal of Medicinal Chemistry, 223, 113638. https://doi.org/10.1016/j.ejmech.2021.113638

  • Gossen J., Albani S., Hanke A., Joseph B. P., Bergh C., Kuzikov M., Costanzi E., Manelfi C., Storici P., Gribbon P., Beccari A. R., Talarico C., Spyrakis F., Lindahl E., Zaliani A., Carloni P., Wade R. C., Musiani F., Kokh D. B. Rossetti G. (2021). A Blueprint for High Affinity SARS-CoV-2 Mpro Inhibitors from Activity-Based Compound Library Screening Guided by Analysis of Protein Dynamics. ACS Pharmacology & Translational Science, 4(3), 1079–1095. https://doi.org/10.1021/acsptsci.0c00215

  • Kuzikov M., Costanzi E., Reinshagen J., Esposito F., Vangeel L., Wolf M., Ellinger B., Claussen C., Geisslinger G., Corona A., Iaconis D., Talarico C., Manelfi C., Cannalire R., Rossetti G., Gossen J., Albani S., Musiani F., Herzog K., Ye Y., Giabbai B., Demitri N., Jochmans D., Jonghe S. D., Rymenants J., Summa V., Tramontano E., Beccari A. R., Leyssen P., Storici P., Neyts J., Gribbon P., Zaliani A. (2021). Identification of Inhibitors of SARS-CoV-2 3CL-Pro Enzymatic Activity Using a Small Molecule in Vitro Repurposing Screen. ACS Pharmacology & Translational Science, 4 (3), 1096–1110. https://doi.org/10.1021/acsptsci.0c00216

  • Zucchiatti P., Birarda G., Cerea A., Semrau M.S., Hubarevich A.,Storici P., De Angelis F., Toma A., Vaccari L. (2021). Binding of tyrosine kinase inhibitor to epidermal growth factor receptor: Surface-enhanced infrared absorption microscopy reveals subtle protein secondary structure variations. Nanoscale, 13(16), 7667–7677. https://doi.org/10.1039/d0nr09200b

  • Annunziato G., Spadini C., Franko N., Storici P., Demitri N., Pieroni M., Flisi S., Rosati L., Iannarelli M., Marchetti M., Magalhaes J., Bettati S., Mozzarelli A., Cabassi C. S., Campanini B., Costantino G. (2021). Investigational Studies on a Hit Compound Cyclopropane–Carboxylic Acid Derivative Targeting O-Acetylserine Sulfhydrylase as a Colistin Adjuvant. ACS Infectious Diseases, 7(2), 281–292. https://doi.org/10.1021/acsinfecdis.0c00378

  • Battista T., Pascarella G., Staid D. S., Colotti G., Rosati J., Fiorillo A., Casamassa A., Vescovi A. L., Giabbai B., Semrau M.S., Fanelli S., Storici P., Squitieri F., Morea V., Ilari A. (2021). Known Drugs Identified by Structure-Based Virtual Screening Are Able to Bind Sigma-1 Receptor and Increase Growth of Huntington Disease Patient-Derived Cells. International Journal of Molecular Sciences, 22(3), 1293. https://doi.org/10.3390/ijms22031293

  • Peleg Y., Vincentelli R., Collins B. M., Chen K.-E., Livingstone E. K., Weeratunga S., Leneva N., Guo Q., Remans K., Perez K., Bjerga G. E. K., Larsen Ø., Vaněk O., Skořepa O., Jacquemin S., Poterszman A., Kjær S., Christodoulou E., Albeck S., Dym, O., Ainbinder E., Unger T., Schuetz, A., Matthes, S., Bader, M., de Marco, A., Storici P., Semrau M.S., Stolt-Bergner P., Aigner C., Suppmann S., Goldenzweig A., Fleishman, S. J. (2021). Community-wide experimental evaluation of the pross stability-design method. Journal of Molecular Biology, 433(13), 166964. https://doi.org/10.1016/j.jmb.2021.166964

  • Ubbiali D., Orlando M., Kovačič M., Iacobucci C., Semrau M.S., Bajc G., Fortuna S., Ilc G., Medagli B., Oloketuyi S., Storici P., Sinz A., Grandori R., de Marco A. (2021). An anti-HER2 nanobody binds to its antigen HER2 via two independent paratopes. International Journal of Biological Macromolecules, 182, 502–511. https://doi.org/10.1016/j.ijbiomac.2021.04.032

  • Pachetti M., Marini B., Benedetti F., Giudici F., Mauro E., Storici P., Masciovecchio C., Angeletti S., Ciccozzi M., Gallo R. C., Zella D., & Ippodrino R. (2020). Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant.Journal of Translational Medicine,18(1), 179. https://doi.org/10.1186/s12967-020-02344-6

  • Cavalloro V., Russo K., Vasile F, Pignataro L., Torretta A., Donini S., Semrau M.S., Storici P., Rossi D., Rapetti F., Brullo C., Parisini E., Bruno O., Collina S. (2020). Insight into GEBR-32a: Chiral Resolution, Absolute Configuration and Enantiopreference in PDE4D Inhibition. Molecules, 25(4), 935. https://doi.org/10.3390/molecules25040935

  • Veggiani G., Giabbai B., Semrau M.S., Medagli B.,Riccio V., Bajc G.,Storici P., de Marco A. (2020). Comparative analysis of fusion tags used to functionalize recombinant antibodies. Protein Expression and Purification,166, 105505. https://doi.org/10.1016/j.pep.2019.105505

  • Soler M.A., Medagli B., Semrau M.S., Storici P., Bajc G, de Marco A, Laio A, Fortuna S.* (2019). A consensus protocol for the in silico optimisation of antibody fragments. Chem Commun 19,14043-14046. doi: 10.1039/c9cc06182g.

  • Rosa B., Marchetti M., Paredi G., Amenitsch H., Franko N., Benoni R., Giabbai B., De Marino M.G., Mozzarelli A., Ronda L., Storici P.*, Campanini B.*, Bettati S. (2019). Combination  of SAXS and Protein Painting Discloses the Three-Dimensional Organization of the Bacterial Cysteine Synthase Complex, a Potential Target for Enhancers of Antibiotic Action. Int J Mol Sci. 20. pii: E5219. doi:10.3390/ijms20205219. 

  • Gobbo D., Piretti V., Di Martino R.M.C., Tripathi S.K., Giabbai B., Storici P., Demitri N., Girotto S., Decherchi S., Cavalli A. (2019). Investigating Drug-Target Residence Time in Kinases through Enhanced Sampling Simulations. J Chem Theory Comput. 15, 4646-4659. doi: 10.1021/acs.jctc.9b00104. Epub 2019.

  • Redenti S., Marcovich I., De Vita T., Pérez C., De Zorzi R., Demitri N., Perez D.I., Bottegoni G., Bisignano P., Bissaro M., Moro S., Martinez A.,Storici P., Spalluto G., Cavalli A., Federico S. (2019). A Triazolotriazine-Based Dual GSK-3β/CK-1δ Ligand as a Potential Neuroprotective Agent Presenting Two Different Mechanisms of Enzymatic Inhibition. ChemMedChem. 14, 310-314. doi: 10.1002/cmdc.201800778.

  • Carlino L., Christodoulou M.S., Restelli V., Caporuscio F., Foschi F., Semrau M.S., Costanzi E., Tinivella A., Pinzi L., Lo Presti .L, Battistutta R., Storici P., Broggini M., Passarella D., Rastelli G.* (2018). Structure-Activity Relationships of
    Hexahydrocyclopenta[c]quinoline Derivatives as Allosteric Inhibitors of CDK2 and EGFR. ChemMedChem. 13, 2627-2634. doi: 10.1002/cmdc.201800687.

  • Raboni S., Revtovich S., Demitri N., Giabbai B., Storici P., Cocconcelli C., Faggiano S., Rosini E., Pollegioni L., Galati S., Buschini A., Morozova E., Kulikova V., Nikulin A., Gabellieri E., Cioni P., Demidkina T., Mozzarelli A.* (2018). Engineering methionine γ-lyase from Citrobacter freundii for anticancer activity. Biochim Biophys Acta Proteins Proteom. 1866, 1260-1270. doi:10.1016/j.bbapap.2018.09.011. 

  • Caporuscio F, Tinivella A, Restelli V, Semrau MS, Pinzi L, Storici P, Broggini M, Rastelli G. (2018). Identification of small-molecule EGFR allosteric inhibitors by high-throughput docking. Future Med Chem. 10(13):1545-1553. doi: 10.4155/fmc-2018-0063. Epub 2018 May 16.

  • Prosdocimi T, Mollica L, Donini S, Semrau MS, Lucarelli AP, Aiolfi E, Cavalli A, Storici P, Alfei S, Brullo C, Bruno O, Parisini E.* (2018). Molecular Bases of PDE4D Inhibition by Memory-Enhancing GEBR Library Compounds. Biochem. Biochemistry. 57(19):2876-2888. doi: 10.1021/acs.biochem.8b00288. Epub 2018 May 1.

  • Stolt-Bergner P, Benda C, Bergbrede T, Besir H, Celie PHN, Chang C, Drechsel D, Fischer A, Geerlof A, Giabbai B, van den Heuvel J, Huber G, Knecht W, Lehner A, Lemaitre R, Nordén K, Pardee G, Racke I, Remans K, Sander A, Scholz J, Stadnik M, Storici P, Weinbruch D, Zaror I, Lua LHL, Suppmann S.* (2018). Baculovirus-driven protein expression in insect cells: A benchmarking study.  J.Struct Biol. 203:71-80. doi: 10.1016/j.jsb.2018.03.004. Epub 2018 Mar 12.

  • Campaner E., Rustighi A., Zannini A., Cristiani A., Piazza S., Ciani Y., Kalid O., Golan G., Baloglu E., Shacham S., Valsasina B., Cucchi U., Pippione A.C., Lolli M., Giabbai B., Storici P., Carloni P., Rossetti G., Bello E., D’Incalci M., Sommaggio R., Cappuzzello E., Rosato A., and Del Sal G. A new covalent PIN1 inhibitor selectively targets cancer cells by a dual mechanism of action; Nat Commun. 2017 Jun 9;8:15772. doi: 10.1038/ncomms15772.

  • Basters A., Geurink P.P., Röcker A., Witting K.F., Tadayon R., Hess S., Semrau M.S. , Storici P., Ovaa H., Knobeloch K-P*, and Fritz G. (2017). Structural basis for the specificity of USP18 towards ISG15. Nature Structural & Molecular Biology, 24, 270-278.

  • Kenig S, Bedolla DE, Birarda G, Faoro V, Mitri E, Vindigni A, Storici P, Vaccari L. (2015) Fourier transform infrared microspectroscopy reveals biochemical changes associated with glioma stem cell differentiation. Biophys Chem.; 207:90-96. doi: 10.1016/j.bpc.2015.09.005. 

  • Ronda L, Bruno S, Bettati S, Storici P, Mozzarelli A. (2015)  From protein structure to function via single crystal optical spectroscopy. Front Mol Biosci.28;2:12. doi: 10.3389/fmolb.2015.00012. 

  • Gianoncelli A, Vaccari L, Kourousias G, Cassese D, Bedolla DE, Kenig S, Storici P, Lazzarino M, Kiskinova M. (2015) Soft X-Ray Microscopy Radiation Damage On Fixed Cells Investigated With Synchrotron Radiation FTIR Microscopy. Sci Rep. 2015 May 14;5:10250. doi: 10.1038/srep10250.

  • Cersosimo U., Sgorbissa A., Foti C., Drioli S., Angelica R., Tomasella A., Picco R., Semrau M., Storici  P., Benedetti F., Berti F., Brancolini C. (2015)  Synthesis, Characterization and Optimization for in Vivo Delivery of a Non-Selective Isopeptidase Inhibitor as New Anti-Neoplastic Agent.  J.Med.Chem. 26;58(4):1691-704. doi: 10.1021/jm501336h. Epub 2015 Feb 12.

  • Bedolla D., Kenig S., Mitri E., Storici P., Vaccari L. (2014) Further insights into G1 and G0 phases of cell cycle revealed by FTIR microspectroscopy. Vib. Spec. 75: 127-135. DOI: 10.1016/j.vibspec.2014.08.007 

  • Bindi S, Fancelli D, Alli C, Berta D, Bertrand JA, Cameron AD, Cappella P, Carpinelli P, Cervi G, Croci V, D'Anello M, Forte B, Giorgini ML, Marsiglio A, Moll J, Pesenti E, Pittalà V, Pulici M, Riccardi-Sirtori F, Roletto F, Soncini C,Storici P, Varasi M, Volpi D, Zugnoni P, Vianello P. (2010). Thieno[3,2-c]pyrazoles: a novel class of Aurora inhibitors with favorable antitumor activity. Bioorg Med Chem. 18, 7113-7120.

  • Beria I, Ballinari D, Bertrand JA, Borghi D, Bossi RT, Brasca MG, Cappella P, Caruso M, Ceccarelli W, Ciavolella A, Cristiani C, Croci V, De Ponti A, Fachin G, Ferguson RD, Lansen J, Moll JK, Pesenti E, Posteri H, Perego R, Rocchetti M, Storici P, Volpi D and Valsasina B. (2010). Identification of 4,5-Dihydro-1H-pyrazolo[4,3-h]quinazoline Derivatives as a New Class of Orally and Selective Polo-Like Kinase 1 Inhibitors. J Med Chem. 53, 3532-3551.

  • Carpinelli P, Ceruti R, Giorgini ML, Cappella P, Gianellini L, Croci V, Degrassi A, Texido G, Rocchetti M, Vianello P, Rusconi L, Storici P, Zugnoni P, Arrigoni C, Soncini C, Alli C, Patton V, Marsiglio A, Ballinari D, Pesenti E, Fancelli D, Moll J. (2007) PHA-739358, a potent inhibitor of Aurora kinases with a selective target inhibition profile relevant to cancer. Mol. Cancer Ther. 6, 3158-3168.

  • Fancelli D, Moll J, Varasi M, Bravo R, Artico R, Berta D, Bindi S, Cameron A, Candiani I, Cappella P, Carpinelli P, Croci W, Forte B, Giorgini ML, Klapwijk J, Marsiglio A, Pesenti E, Rocchetti M, Roletto F, Severino D, Soncini C,  Storici P, Tonani R, Zugnoni P, and Vianello P (2006) 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles: Identification of a Potent Aurora Kinases Inhibitor with a Favorable Antitumor Kinase Inhibition Profile, J Med Chem 49, 7247-7251.

  • Soncini C, Carpinelli P, Giannellini L, Fancelli D, Vianello P, Rusconi L, Storici P, Zugnoni P, Pesenti E, Croci V, Ceruti R, Giorgini ML, Cappella P, Ballinari D, Sola F, Varasi M & Bravo R (2006),  PHA680632, a novel Aurora kinase inhibitor with potent antitumoral activity. Clin.Cancer Res. 12, 4080-4090.

  • Baslé A, Rummel G, Storici P, Rosenbusch J.P .and Schirmer T (2006), X-ray crystal structure of osmoporin OmpC from E. coli at 2.0 Å. J.Mol.Biol. 362, 933-942

  • Fancelli D, Berta D, Bindi S, Cameron A, Cappella P, Carpinelli P, Catana C, Forte B, Giordano P, Giorgini ML, Mantegani S, Marsiglio A, Meroni M, Moll J, Pittala V, Roletto F, Severino D, Soncini C, Storici P, Tonani R, Varasi M, Vulpetti A, Vianello P. (2005) Potent and selective aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition. J Med Chem. 48, 3080-3084.

  • Storici P, Qiu J, Schirmer T, Silverman RB. (2004) Mechanistic crystallography. Mechanism of inactivation of gamma-aminobutyric acid aminotransferase by (1R,3S,4S)-3-amino-4-fluorocyclopentane-1-carboxylic acid as elucidated by crystallography. Biochemistry 43, 14057-14063.

  • Storici P., De Biase D., Bossa F., Bruno, S., Mozzarelli A., Peneff C., Silverman R.B. and Schirmer T. (2004) Structures of g-aminobutyric acid (GABA) aminotransferase, a pyridoxal 5'-phosphate, and [2Fe-2S] cluster-containing enzyme, complexed with gamma-ethynyl-GABA and with the antiepilepsy drug vigabatrin. J Biol Chem. 279, 363-373.
     

Last Updated on Monday, 09 January 2023 16:05